`
`CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`21-660
`
`ADMINISTRATIVE DOCUMENTS
`
`CIPLA EXHIBIT 1016
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`Page 1 of 102
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`CIPLA EXHIBIT 1016
`Page 1 of 102
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`

`American BioScience, Inc.
`
`N21660
`
`'
`
`American BioScicncm Inc.
`
`Patent Certification
`
`Paragraph II Certification
`
`In the opinion and to the best knowledge of American BioSeience, 1110., there are-no
`
`unexpired patents {mu claim the listed drug ['[‘axol® (paelitaxel) Injection] referred to
`
`in this application or that claim a use of the listed drug.
`
`Mitchall G. Clark
`
`Date
`
`Vice President, Regulatory Affairs
`
`2730 Wilshire Blm.. in}. u: 110 Santa Monica, California 90403 Tel: (310) 883-1300 Fax: (310) 998-8553
`
`CIPLA EXHIBIT 1016
`
`Page 2 of 102
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`CIPLA EXHIBIT 1016
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`
`
`American BioScience. Inc.
`
`N21660
`
`i
`
`-
`=
`Department of Health and Human Sconces
`Food and Drug Adn'unlstration
`PATENT INFORMATION SUBMITTED WITH THE
`FILING OF AN NDA, AMENDMENT, 0R SUPPLEMENT
`For Each Patent That Claims a Drug Substance
`(Active Ingredient), Drug Product (Fonnuiation and
`Composition) and/or Method of Use
`
`Form Approved10MB No. 0310-0513
`wmmn Dam: 07mm
`See OMB Statementon Page 3‘
`ND. amen
`
`NAME OF APPLICANT I NBA HOLDER
`American BioScicnoe. [no
`
`The following is provided in accordance with Section 505(k) and (c) of the Federal! Food Drug. and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME}
`AbraxaneTM (nab Paclltaxet) for [in ectable Suspenston
`ACTIVE INGREDIENHS]
`Pactitaxel
`
`STRENGTHtS}
`100 mg/vial
`
`DOSAGE FORM
`Sterile powder for injectable suspension
`
`required to be submitted to the Food and Dmg Administration (FDA) with an NBA application.
`This patent declaration form is
`amendment. or eupptement as required by 21 CFR 314.53 at the address provided in 21 CFR 314.53(d)(4}.
`Within thirty (30) days after approval of an NBA or supplement. or within thirty (30) days of issuance of a new patent. a new patent
`declaration must be submitted pursuant to 21 CFR 314.53tc)(2)(ii) with all of the required information based on the approved NDA
`or supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied
`upon by FDA for listing a patent in the Orange Book.
`
`For hand-written or typewriter version: (only) of this report: It additional space is required for any narrative answer (i.e.. one
`that does not require a "Yes“ or "No“ response). please attach an additional page referencing the question number.
`FDA wiii not list patent information if you file an incomplete patent declaration or the patent declaration indicates die
`patent is not eitgibie for listing.
`
`For each patent submitted for the pending NBA, amendment, or supplement referenced above, you must submit all the
`infon'nation described beiow. if you are not submitting any patents for this pending NBA. amendment. or supplement,
`iota above section and sections 5 and 6.
`
`a. United States Patent Number
`6,537,579
`d Name oi Patent Owner
`American BioScience, inc.
`
`V
`
`b. issue Data of Patent
`3/25/2003
`Address (of Patent Owner)
`2730 Wilshire Boulevard, Suite 110
`
`-
`
`c. Expiration Date ref-Patent
`2023013
`
`‘
`
`
`
`Cityistate
`Santa Monica, CA
`ZIP Code
`90403
`
`Telephone Number
`3 [0 883 1300
`
`FAX Number (ifsvaiiebie)
`3 to 998 8553
`
`E-Mail Address (ifavaiiabia)
`
`e. Name at agent or repgeflgtatiy who resides or maintains Address (of agent ormprasentative namedin 1.5.)
`a place or business within the United States authorized to
`receive notice of patent codification under section
`505(b)(3} and (j)(2)(B) of the Federal Food, Drug. and
`Cosmetic Act and 21 CFR 314.52 and 314.95 (it patent
`owner or MBA appficantiholder does not reside or have a
`place of business within the United States)
`
`CWS‘E‘F
`
`G: NIA
`
`Telephone Number
`
`FAX number (If sullen”)
`
`E—Mail Address (it avaiiabie)
`
`t.
`
`Is the patent referenced above a patent that has been submitted previously for the
`approved NBA or supplement referenced above?
`g it the patent referenced above has been submitted previously for listing. is the expiration
`date a new expiration date?
`
`FORM FDA 3542a (7103)
`
`Page 1
`PSC Ml!" mull) NJ-Im EI’
`
`
`
`22
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`CIPLA EXHIBIT 1016
`
`Page 3 of 102
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`CIPLA EXHIBIT 1016
`Page 3 of 102
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`American BioScience, inc.
`
`N21660
`
`For the patent referenced above, provide the following information on the drug substance, drug product andfor method of
`use that is the subject of the pending NBA, amendment, or supplement.
`
`
`,
`_ _.
`2. £5qu subsist-r 1M0 Ill”:
`2.17Doesthe patent claim the drug substance thatis the active ingredient'in the drug product
`described'In the pending NBA. amendment, or supplement?
`2.2 Does the patent daim a drug substance that is a different polymorph oi the active
`ingredient described in the pending NBA. amendment. or Iuppiement?
`2.3 It the answer to question 2.2 is “Yes." do you certify that, as of the date of this declaration. you have test data
`demonstrating that a dmg product containing the poiyrnorph wilt perfon-n the some as the drug product
`described in the NBA? The type of test data required is described at 21 CFR 314.530”.
`2.4 Specify the potymomhii: torm(s) claimed by the patent forwhich you have the test results described in 13.
`
`C] Yes
`
`2.5 Does the patent claim onty a metabolite oi the active ingredient pending in the MBA or supplement?
`(Complete the inlalmation in section 4 below if the patent claims a pending method of using the pending
`drug product to administer the metabolite.)
`2.6 Does the patent claim only an inter-mediate?
`
`D Yes
`
`{XI No
`
`2.7 It the patent referenced in 2.1 is a product-hy-prooess patent. is the product claimed in the
`patent novel? (An answer is required only it the patent is a produd-hy-process patent.)
`
`3.;Di'ug Pioaumtconpostaomfionéiuiiubn)
`3.1 Does the patent claim the drug product. as defined in 21 CFR 314.3, in the pending NBA,
`amendment. or supplement?
`3.2 Does the patent claim only an intermediate?
`
`3.3
`
`It the patent referenced in 3.1 is a productvbyprooest patent. is the product claimed in the
`patent novel? (An answer is required only it the patent is a product—by-pmcess patent.)
`
`
`
`4. Method amt.
`Sponsors must submit the information in section 4 separateiy hr each patent claim claiming a method of using the pending drug
`product for which approval is being sought. For each mottled ofuse claim referenced. provide the following information:
`4.1 Does the patent claim one or more methods of use tor which approval is being sought In
`the pending NDA. amendment. orsupplemenl?
`L2 Patent Claim Number (as iisiedin the patent)
`[-6. 10.| 5. 22.27, 3{J.421 49.5|
`
`E Yes
`Does the patent cla‘m referenced in 4.2 claim a pending method
`at use forwhlch approval I: being sought in the pending NBA,
`amendment. or supplement?
`E Yes
`
`[I No
`
`D No
`
`FORM FDA 3542a (HOS)
`
`Page 2
`Isom- MlODHMS—IDW EF
`
`
`
`23
`
`CIPLA EXHIBIT 1016
`Page 4 of 102
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`CIPLA EXHIBIT 1016
`Page 4 of 102
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`

`

`American BioScience. inc.
`
`N21660
`
`i
`
`‘18 lithe answer to 4.2 is
`“Yes." identify with speci‘
`ticity the use with retor-
`cnoo to the proposed
`labeling for the dmg
`product.
`
`Use: (Submit irrdr'cetr‘on ormettrod or use information as identified spectficeiryr'n dre approved labeling.)
`Claims 10-15 - Abraxane (nob paclitamt) tor inlectable suspension is a nlnuparticlu alhwnin-bound (nab) term of
`paclitaxel. See Description. Each single-use vial contains 100 mg oi pacitaxel and approximately 900 mg of human
`albumin. See Descnm'on.
`‘I'l'u's ion'nulation is tree from solvents. See Desmptia'r. Abraxane (nab paciitaxel) for
`injectable suspension is indicated for the treatment «mm cancer. See indication. Aoraxane does not
`contain Cremophor-EL. therefore hypersensitivity rea on! Abraxane are rare. See Adverse Reactims:
`Hypersensitivity Reactions (HSRs). For metastatic breast cancer. Abraxane (nab pacl‘rtercei tor injectable suspension)
`at a dose of 260 mgim administered intravenously over 30 minutes every 3 weeks has been chm to be effective.
`See Dosage and Administration.
`
`Claims 22-27. 32-34. 39-42. and 49.51 - Abmxane (nab paclitaxel) tor iniectabie suspension is a nanomnicle albumin-
`bound (nab) form of nutritional. See Desorption Marlene is supplied as a white to yellow. sterile. Iyophlllzed we:
`intended for reconstitution w'flh 0.9% Sodium Chloride iniection. USP prior to intravenous mtusion. See Descrbtr‘on.
`Each singleme vial contains 100 mg of paclitaxel and approximately 900 mg of human athun'lin. See Description.
`Abraxane (nab pactilaxel) tor injectable suspension is indicated tor the treatment of “breast cancer. See
`indication. For metastatic breast cancer. Abraxane (nab paclitarret for lniectable suspension) at a dose of 260 mgfm‘
`administered intravenously over 30 minutes every 3 weeks has been shown to be otteclive. See Dosage and
`Administration. Abraxane is supplied as a sterile tyophlfized powder for reconstitution before use. See Dosage and
`Administration: Preparation for intravenous Administration. Reconstitute each vial by injecting 20 mL of 0.9% Sodium
`Chloride Iniectiorl. USP. $90 003599 and Administration: Preparation for intravenous Administration. Each mL at the
`reconstituted nanoparticle formulation will contain 5 mgimL paciitaxel. See Dosage and Administration: Preparation for
`intravenous Administration.
`
`
`
`Claim 30 - Abraxane [nab paclitaxet] for iniectabie suspension is a nanopanicte albumin—bound (nab) term at paciitaxel.
`See Descnpfion. Each single-use vie! contains 100 mg of pactitaroel and apprordmatety 900 mg of human albumin.
`See Description. This formulation is free from solvents. See Description. Abraxane (nab paclitaxel) tor lniectabie
`suspension is indicated for the treatment eluted“ cancer. See indication. Neutropenia. the most important
`hematologic toxicity. was dose dependent and was generally rapidly reversible. See Adverse Reactions: Hematologic.
`Grade 4 (<500 cellslrnm’) neutropenia occurred in 12% of patients treated with Abraxane See Adverse Reactions:
`Hematologic.Among patients treated in the Phase 3 metastatic breast cancerstudy. neutrophii counts declined below
`500 cellsimrn (Grade 4)in 9% of the patients treated with a dose of 260 mgi'm‘ compared to 2256'in patients receiving
`Cremephonbased paclitaxei Injection at a dose of 175 motor“. See Adverse Reactions: Hematologic. Among patients
`Abraxane does not contain Cremophor~EL. therefore hypersensitivity reactions to Abraxane are rare. See Adverse
`Reactions: Hypersensib'vr'ty Reactions (HSRs). For metastatic breast cancer. Abraxane (nab paciitaxel for injectabio
`suspension) at a dose ct 260 mgiin administered intravenousiy over 30 minutes every 3 weeks has been shown to be
`effective. See Dosage and Administration. AbraJrane'is supplied as a sterile tyophiiized powder for reconstitution
`before use. See Dosage and Administration: Preparation for intravenous Administration. Reconstitute each vial by
`interning 20 mL of 0.9% Sodium Chloride Intention. USP. See Dosage and Administration: Preparation fortntravenous
`Administration.
`
`Claim 31 ~ Abraxane (nab paclitaxei) tor injectable suspensioniis a nanoparticle albumin-bound (can) term of
`paciitaxet. See Description. Each single-use trial contains 190 mg of paclttaxel and approximately 900 mg of human
`albumin. See Description. Abraxane (nab paclitaxeli tor injectabie suspension is indicated for the treatment oi
`mowed cancer. See indication.
`in general. the frequency and severity oi neurotogic manifestations were
`ependent in patients receiving single-agent Abraxane. See Adverse Reactions: Neurologic. Peripherat
`neuropathy was observed in 64% of all patients (10% severe). See Adverse Reactions: Neurologic. Peripheral
`neuropathy was the cause of Abraxane discontinuation in 135366 (4%) at all patients. See Adverse Reactions:
`Neumtogr‘c. Sensory symptoms have usually improved or resolved within 22 days or interrupting Abram therapy.
`See Adlrerse Reactions: Neurologr'c. Pro-existing neuropathies resulting from prior therapies are not a contraindication
`For Abraxene therapy. See Adverse Reactions: Neumlogic. No incidences of grade 4 peripheral neuropathies were
`reported in the clinical trial. See Adverse Rsections:Nsuroiogr'c. Other than peripheral neuropathy. serious neurologic
`events following Abruane administration have been rare (<1%) and have hrcluded ischemic stroke metabolic
`encephalopathy. confusion. dinlnessilightheadedness. and mood alterationldepression. See Adverse Reactions:
`Neurotogic. For metastatic breast cancer. Abraxane (nab paclitaxel tor lnjectebie suspension) at a dose at 260 mgim’
`administered intravenously over 30 minutes every 3 weeks has been shown to be ettective. See Dosage and
`Administration. Abraxane is supplied as a sterile lyopltitized powder for reconstitution before use. See Dosage and
`Administration: Preparation for intramnous Adminisoatr'on. Reconstitute each via! by injecting 20 mL at 0.9% Sodium
`Chloride Injection. USP. See Dosage and Administration: Preparation fortntravenous Administration.
`
`FORM FDA 3542a (”03)
`
`Page 3
`55C Mull: moonlit-rm F5
`
`
`
`24
`
`CIPLA EXHIBIT 1016
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`CIPLA EXHIBIT 1016
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`

`

`American BioScience, Inc.
`
`N21660
`
`4.2a it the answer to 4.2 is
`Use: (Submit indication ormothod of use lnfonnetion as identified specifically in the approved labeling.)
`
`
`
`'Yes.‘ identify with speci-
`Claims 36 and 33 -Abrexane (nab pacfilmrel) for intractable suswnslon is l nanoparticle olbmn‘m—bound (nab) form of
`
`
`
`ficfiY “ll-'- “33 With refer—
`paclitaxel. See Descrmhm. Abraxene is supplied as a while to yellow. Itenle. tyophllized powder intended for
`
`
`
`0009‘“) the Proposed
`reconstitution with 0.9% Sodium Chloride Inhabit. USP prior to intravenous infusion. See Description. Each single-
`
`
`
`IaMINI for the drug
`use vial contains 100 mg of paclitanel and approximately 900 mg of human albumin. See Description.
`
`
`
`product.
`Two studies were conducted in 106 patients previously treated with a maximum of one prior chemotherapeutic
`
`
`regimen. See Clinical Studies: Breast Cenfinome: Phase 2 open label studies Abramne was administered in these
`
`
`
`two trials as a 30 minute infusion at doses of 175 Inglrn or 300 mglm‘ without steroid premedication or planned G-
`CSF support. See Clinical StudI'es Breast Carcimma: Phase 2 open iabelstudies. Abramne (nab psclitexel tor
`
`
`
`injectable suspension) is indicated for the treatment ofwbreast cancer. See indication. For metastatic breast
`
`
`cancer Abrexane (neb-peclitaxel for injocleblo suspension) at a dose of 260 motor: administered intravenously over 30
`
`
`minutes every 3 weeks has been shown to be effective See Dosage and Administration Abraxene is supplied as a
`
`
`sterile lyophilized powder for reconstitution belere use. See Dosage and Adminlsb'ation: Preparation lulntrewnous
`
`
`Administration. Reconstitute each vial by inhaling 20 mL of 0.9% Sodium Chloride Inledlon. USP. See Dosage and
`
`Administration: Preparation for intravenous Administration. No premedioalion is required prior to the administration of
`
`
`Abrmne. See Dosage and Administration: Preparation and Adminisuetion Precautions.
`
`
`
` 5. No Relevant Patents
`
`For this pending NDA. amendment. or supplement. there are no relevant patents that claim the drug substance (active ingredient).
`
`
`drug product (formulation or composition) or method“) of use, for which the applicant ls seekhtg approval and with respect to
`
`
`
`[3 YES
`which a claim of patent infringement could reasonably be asserted ifa person not licensed by the owneroftho patent engaged in
`the manufacture. use. or sale ofthe drug product.
`
` 6. Declaritlon Certification
`
`a.1 The undersigned declares that this is an accurate and complete submission ofpatent information for the NBA.
`
`
`amendment. or supplementpending under section 505 of the Federal Food, Drug. and Cosmetic Act. This time-
`
`senslttvo patent lnfonnao'on is submittedpursuant to 21 CFR 314.53. lattes: that i am familiar with 2! CFR 314.53 and
`fills submission complies with the requirements of the regulation. lverlfy under penalty ofperjury that the foregoing
`
`
`is true and correct.
`Wanting: A willfully and knowingly false statement is a criminal offense under 18 U.S.C. 1001.
`
`
`Date Signed
`6.2 Authorized Signature of NBA ApplicantlHolder or Patent Owner (Attorney. Agent, Representative or
`
`
`
`other Authorized Official) P ..
`'- . lnt'mnetion below)
`
`
`
`Bioscience, inc.
`Patrick Soon-Shiong, M ,
`
`
`/3 MM;
`
`
`ey submit this declaratlon directly to the FDA. A patent owner who Is not the NDA opplicantl
`NOTE: Only an NBA applicantlholdor
`
`holder is authorized to sign the doctoral no but may not submit It directly to FDA. 21 CFR 314.5333“) and (dim.
`
`
`E NDA Applicant/Holder
`
`C] NDA Applicant'slHolder‘s Attorney. Agent (Representative) or other
`Authorized Official
`
`Check applicable box end provide information below.
`
`
`
`
`
`[:| Patent Owner
`
`_
`Name
`American BioScience, Inc.
`Address
`2730 Wilshire Boulevard. Suite llti
`
`ZIP Code
`90403
`
`I3 Patent Owners Attorney. Agent (Representative) or Other Amhorized
`Official
`
`Cityistate
`Santa. Monica. CA
`
`Telephone Number
`310 833 1300
`
`
`
`
`
`FAX Number (ll available)
`E—Mail Address (if available)
`310 998 8553
`
`
`
`
`FORM FDA 35423 (7103)
`
`Page 4
`“CM-II. mam: eel-Ion
`E?
`
`
`
`25
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`

`American BioScience, Inc.
`
`N21660
`
`An agency may not cmduct or sponsor, anda person is no! nquired to amendto. a collection of
`
`lhis coilection of infotmuion has been estimated to Iva-age 9 hours per name. including the time for reviewing
`The public reporting burden Ibu-
`instructions, searching existing data sources. gathering and maintaining the dun nwdcd. and oomph-fins and reviewing the collection of infirm-(ion. Send
`mt; reg-Ming this burden urinate or my other aspect mm: collection ofinfotmntion. including suggestions for Iuiucing this burden to:
`Food and Drug Administration
`CDER (HFMOT)
`5600 Fishers lane
`Roclwille. MD 10857
`
`infirmflau auricu- ir displqwa cmdy valid OMB control number.
`
`FORM FDA 3542a {1:03)
`
`Pa e sa
`PSC Mdil Magnum-1w Er
`
`
`
`26
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`

`American BioScience, lnc.
`
`N21660
`
`INFORMATION AND INSTRUCTIONS FOR FORM 3542a
`
`PATENT INFORMATION SUBMITTED WITH THE FlLlNG
`OF AN NDA, AMENDMENT OR SUPPLEMENT
`
`describes the authorized signature.
`
`General Information
`
`information to the agency the appropriate
`0To submit patent
`patent declaration form must be used. Two forms are available
`for parent submissions. The approval status of your New Drug
`Application will determine which form you should use.
`patent
`a Form 3542a
`should
`be
`used when
`submitting
`information with original NDA submissions. NDA amendments
`and NBA Suppleman prior to approval.
`
`supplemental
`IForm 3542 should he used after NDA or
`approval. This form is to be submitted within 30 days after
`approval of an application. This form should also be used to
`submit patent
`information relating to an approved supplement
`under 2] CFR 314.53(d) to change the formulation, add a new
`indication or other condition of use, change the strength, or to
`make any other patented change regarding the drug, drug
`product, or any method of use.
`
`OForm 3542 is also to be used for patents issued after drug
`approval. Patents issued after drug approval are required to be
`submitted within 30 days of patent issuance for the patent to be
`considered "timely filed."
`
`IOnly information fi'orn form 3542 will be used for Orange
`Book Publication purposes.
`I Forms should be submitted as described in 2t CFR 314.51 An
`additional copy of form 3542 to the Orange Book Staff will
`expedite patent publication in the Orange Book. The Orange
`Book Staff address (as of July 2003) is: Orange Book Staff,
`Office of Generic Drugs OGDJHFD-Glo, 7500 Standish Place,
`Rockville, MD 20855.
`
`- The receipt date is the date that the patent information is date
`stamped in the central dOCumenr room. Patents are considered
`listed on the date received.
`
`0 Additional copies of these forms may be downloaded from the
`[memet at: http://{arma are. gav/(onns/‘pja‘ahtm/[dahrmhim l.
`First Section
`
`Complete all items in this section.
`I. General Section
`
`Complete all
`itself.
`
`items in this section with reference to the patent
`
`lc)
`
`Include patent expiration date, including any Hatch-Waxman
`patent extension already granted. Do not
`include any
`applicable pediatric exclusivity. The agency will
`include
`pediatric exclusivities where applicable upon publication.
`
`id)
`
`Include full address of patent owner. If patent owner resides
`outside the U. S. indicate the country in the zip code block.
`
`le)
`
`Answer this question ifapplicable. If patent owner and NBA
`applicantlholder reside in the United States,
`leave space
`blank
`
`2. Drug Substance (Active Ingredient)
`
`Complete all items in this section if the patent claims the drug
`substance that is the subject of the pending NDA, amendment, or
`supplement.
`
`2.4) Name the polymorphic form of the drug identified by the
`patent.
`
`2.5) A patent for a metabolite of the approved active ingredient
`may not be submitted. If the patent claims an approved
`method of using the approved drug product to administer
`the metabolite the patent may be submitted as a method of
`use patent depending on the responses to section 4 of this
`form.
`
`2.7) AttSwer this question only if the patent
`proeess patient
`
`is a product-by-
`
`3. Drug Product (Composition/Formulation)
`
`items in this section if the patent claims the drug
`Complete all
`product that is the subject of the pending NDA, amendment1 or
`supplement.
`
`3.3) An answer to this question is required only if the referenced
`patent is a product-by—pmoess patent.
`4. Method of Use
`
`Complete all items in this section if the patent claims a method of
`use of the drug product that is the subject of the pending NDA,
`amendment. or Supplement.
`
`42)
`
`identity by number each claim in the patent that claims the
`use(s) of the drug for which approval
`is being sought.
`Indicate whether or not each individual claim is a claim for
`a. method(s) of use of the drug for which approval is being
`sought.
`
`4.2a) Specify the part of the proposed drug labeling that
`claimed by the patent
`
`is
`
`5. No Relevant Patents
`
`Complete this section only ifapplicable.
`6. Declaration Certification
`
`Complete all items in this section.
`
`6.2) Authorized signature. Check one of the four boxes that best
`
`FORM FDA 35428 (7103)
`
`Page 6
`rec MdllMaflDlllll-lm I-‘.t-‘
`
`
`
`27
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`

`
`
`American BioScience, Inc.
`
`N21660
`
`Department of Health and Human Services
`.
`.
`.
`Food and Drug Administration
`PATENT INFORMATION SUBMITTED WITH THE
`FILING OF AN NDA, AMENDMENT, OR SUPPLEMENT
`For Each Patent That Claims a Drug Substance
`(Active ingredient), Drug Product (Formulation and
`Composition) and/or Method of Use
`
`FM" ”Wm.“ 0”” "“1910 D513
`Expiration Date: 07i31i06
`3” 0MB 8mm”, Page 1
`
`21.660
`NAME OF APPLICANT! NBA HOLDER
`American BioScicucc, Inc.
`
`The following is provided in accordance with Section 505(k) and (c) of the Federal Food. Drug, and Cosmetic Act.
`TRADE NAME (OR PROPOSED TRADE NAME)
`Abraxanem (nob Paclitaxel) for Lnjectabie Suspension
`ACTIVE INGREDlENTtS)
`Paclitaxel
`
`STRENGTHtS)
`lOO rug/vial
`
`DOSAGE FORM
`Sterile powder for injectable suspension
`
`required to be submitted to the Food and Drug Administration (FDA) with an NBA application,
`This patent declaration form is
`amendment, or supplement as required by 21 CFR 314.53 at the address provided in 21 CFR 314.53ldti4).
`Within thirty (30) days after approval at an MBA or supplement, or within thirty (30) days of issuance of a new patent. a new patent
`declaration must be submitted pursuant
`to 21 CFR 314.53(c)(2)(ii) with all of the required information based on the approved NDA
`or supplement. The information submitted in the declaration form submitted upon or after approval will be the only information relied
`upon by FDA ior listing a patent in the Orange Book.
`
`For handwritten or typewriter versions (only) of this report: if additional space is required for any narrative answer (i.a., one
`that does not require a "Yes” or "No' response). please attach an additional page reterencing the question number.
`
`FDA will not list patent information it you file an incomplete potent declaration or the patent declaration indicates the
`patent. is not eligible for listing.
`_-__——_——————I———————
`For each patent submitted for the pending NBA. amendment, or supplement referenced above. you must submit all the
`information described below. if you are not submitting any patents for this pending NDA, amendment. or supplement.
`lete above section and sections 5 and 6.
`
`‘
`
`C
`
`.
`,
`b. Issue Date of Patent
`111412003
`Address (olPeteni Owner)
`2730 Wilshire Boulevard, Suite 1I0
`
`J
`-
`c. Expiration Date of Patient
`2.9212013
`
`'
`
`-
`
`FAX Number (ifsveilabio)
`Bill] 993 3553
`
`EMaitAddress (it available)
`
`Address (of agent or representative named in 1.9.)
`
`
`
`1.6ENERAL
`a. United States Patent Number
`6,506,405
`d. Name 01 Patent Owner
`American BioScicnce, Inc.
`
`e. Name gt agent or representative who reside: or maintains
`a place at business within the United States authorized to
`receive notice of patent codification under section
`505MB) and (SIRIUS) of the Federal Food, Drug. and
`GosrneticAct and 21 era 314.52 and 314.95 (it patent
`owner or MBA applicantihotder does not reside or have a
`place of business within the United States)
`0-, Nm
`
`CityiState
`Santa Monica, CA
`ZIP Code
`90403
`
`Telephone Number
`310 883 1300
`
`_
`CW5!“
`
`ZlP Code
`
`Telephone Number
`
`f.
`
`Is the patent reierenced above a patent that has been submitted previously for the
`approved NDA or supplement referenced above?
`9. If the patent referenced above has been submitted previously for listingI is the expiration
`date a new expiration date?
`
`FORM FDA 3542a (7103}
`
`FAX Number {if available)
`
`E-Mail Address (if evaiiabiel
`
`D Yes
`
`E No
`
`D Yes
`
`D No
`
`Page 1
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`For the patent referenced shove provide the following information on the drug substance. drug product and/or method of
`use that is the subject of the pending NBA. amendment. orsupplement.
`2.Dotti sub;Encai3int
`._
`.
`.
`t
`2.1 Does the patent claim the drug substance that"re the active ingredientin the drug product
`described in the pending NDA. amendment, or supplement?
`2.: Does the patent claim a drug substance that is a dirterent potymorph otthe active
`ingredient described in the pending NDA. amendment. or supplement?
`2.3 It the answer to question 2.2 ls 'Yes,‘ do you certify that. as of the date of this declaration, you have test data
`demonstrating that a drug product containing the polymotph will pertorm the some as the drug product
`described in the NBA? The type of test data required is described at 21 CFR 314.52%).
`2.4 Specify the polymorphic fOI‘I‘I'I(S) claimed by the patent for which you have the test results described in 2.3.
`
`2.5 Does the patent claim only a metabolite of the active ingredient pending in the NDA or supplement?
`(Complete the lntomtatton in section 4 below if the patent claims a pending method of using the pending
`drug product to administer the metabolite.)
`2.6 Does the patent claim only an intermediate?
`
`CI Yes
`
`2.? lithe patent referenced in 2.1 is a product-by-process patent, is the product claimed in the
`patent novel? (An answer is required only it the patent is a product-hy—ptocess patent.)
`
`.
`3 Drug.Product [Compositioanor-mulntion)
`3.1 Does the patent claim the drug produd as defined'in 21 CFR 314.3 in the pending NDA
`amendment. or supplement?
`3.! Does the patent claim only an intermediate?
`
`3.3 It the patent referenced in 3.1 is a product-by—process patent. is the product claimed in the
`patent novel? (An answer is required only if the patent is a product-by-prooess patent.)
`
`4. Method of Use
`
`Yes DNo
`
`Sponsors must submit the information in section 4 separately for each patent claim claiming a method of using the pending drug
`product for which approval is being sought. For each method of use claim referenced provide the following information:
`4.1 Does the patent claim one or more methods of use tot which approval is being sought in
`the pending NDA, amendment or supplement?
`4.2 Patent Claim Number (as listed in the patent)
`13—22, 24-34, 36—40, 44, 46, 4B, 52, 54. 56,
`58, 60
`
`E Yes
`Does the patent claim referenced in 4.2 claim a pending method
`0‘ use for Which approval is being songht in lhe pending NBA.
`amendment" Dl' supplement?
`
`EINo
`
`
`
`American BioScience, inc.
`
`N21660
`
`FORM FDA 35423 (”03)
`
`Page 2
`)SCMAi-MIIHDIHfl-IWD EF
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`American BioScience, Inc.
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`N21660
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`
`4.2: if the answer to 4.2 is
`Use: (Submit ir'rdicattbn ormethodofuae information as Identified specifically-h b‘ro approved floating.)
`
`
`'Yes.‘ identity with speci—
`Claims 13-22. 2446. 33-34. 35. 37-40. 44. 46. 4B. 54. and 55 -Abraxane (nab positional) tor injeotable suspension is a
`
`
`nsnopanicie answer-boom (nab) form of pacfitasel. See Description. Each single-me vial contains too mg or
`ficity the “39 Willi “ti"-
`
`
`
`once to the proposed
`pacing-gel and approximately 900 mg of human albumin. See Dasa'fption. Thh formulation is free from solvents. See
`
`
`
`Iaboihv forlhe druv
`Description. Abraxane (nab paclitaxel') for injectable suspension is lndimted forthe treatment utmost
`
`
`
`product.
`cancer. See indkration. Abmrcane does not contain Cremophor-EL. therefore hypersensitivity reactions to Abmane
`were rare. See Adverse Reactions: Hypersensitivfb' Reactions (HSRs). For metastatic breast cancer. Antenna (neb-
`
`
`paclitaxef for injectabie suspension) at a dose of 260 motm‘ administered intravenously over 30 minutes every 3 weeks
`has been shown to be effective. See Dosage and Administration. No premedication is required prior to the
`
`
`administration of Abmxane. See Dosage and Administration: Preparation and Administration Precautions.
`
`
`
`Claims 27-29 - Abraxane (nab paclitaxel) for injectabfe suspension is a nanoparticle albumin~bound (nab) form at
`
`
`pactitaxel. See Description. Each single-use vial contains 100 mg of paciitaxet and approximately 900 mg of human
`albumin. See Description. This formulation has from solvents. See Description. Aerator-re (nab paclitarrei tor
`
`
`lniectable suspension) is indicated for the treatment of” breast car-oer. See indication. Abraxane does not
`
`
`contain Cremophor-EL. theretore hypersensitivity reactions to Abraxane were rare. See Adirerse Reactions:
`
`
`Hypersensitivity Reactions (HSRsJ. Nettropenla. the most important hematologic toxicity. was dose dependent and
`
`
`was generally rapidly reversible. See Adverse Reactions: Hematologic. Grade 4 ((500 oettefmm’) neutropania
`
`
`occurred in 12% of patients treated with Abtaxano. See Adverse Reactions: Hematologic. Among patients treated in
`
`
`the Phase 3 metastatic breast cancer study. neutmphll counts declined below 500 cellsimrn' (Grade II) in 9% of the
`
`
`patients treated with a dose of 260 mgrm1 compared to 22% in patients receiving Gramophcr-based paclitaxel iniection
`
`
`at a dose of 175 mgi‘m‘. See Adwrse Reaciims: Hematologic. For metastatic breast cancer. Abmxane (nab
`
`
`pactitaml for inleotabie suspension) at a dose of 260 rngtirl'lI administered intravenously over 30 minutes every 3 weeks
`
`
`has been shown to be effective. See Dosage and Administration.
`
`
`
`
`Claims 30-32 - Abruane (nab pact‘rtaneil for lniectahio suspension is a nenoparticle albumin-bound (nap) form of
`
`
`paclitaxel. See Description. Each single-use vial contains 100 mg of paclitaxei and approximately 900 mg of human
`albumin. See Desorption. This formulation is tree from solvents. See Description. Abrarrane (nab pactaaxel) for
`
`
`injectable suspension Is indicated for the treatment omen cancer. See indication.
`In general. the
`
`
`frequency and severity of neurologic manifestations were dose-dependent in patients receiving single-agent Abraxane.
`
`
`See Adverse Reactions: Neurologic. Peripheral nouropathy was observed in 64% of all patients (10% severe). See
`
`
`Adverse Reactions: Neuroiogrc. Peripheral neuropathy was the cause at Abraxane discontinuation in 131366 {4%) of
`
`
`all patients. See Adverse Reactions: Neurologic. Sensory symptoms have usually inproved or resolved within 22
`days of interrupting Ahraxane therapy. See Adverse Reactions: Neurorogic. Pro-existing neuropathles resulting from
`
`
`prior therapies are not a contraindication for Abraxane therapy. See Adverse Reactions: Neurotogr'c. No incidences at
`
`
`grade 4 peripheral neuropathies were reported in the clinical trial. See Adverse Reactions: Neurobgic. Other than
`
`
`peripheral neuropathy. scriOus neuro